Discussion of the selection and use of teaching aids and standard materials in the lower school at Perkins School for the Blind

Thesis (Ed.M.)--Boston Universit

Expression of a large LINE-1-driven antisense RNA is linked to epigenetic silencing of the metastasis suppressor gene TFPI-2 in cancer

LINE-1 retrotransposons are abundant repetitive elements of viral origin, which in normal cells are kept quiescent through epigenetic mechanisms. Activation of LINE-1 occurs frequently in cancer and can enable LINE-1 mobilization but also has retrotransposition-independent consequences. We previously reported that in cancer, aberrantly active LINE-1 promoters can drive transcription of flanking unique sequences giving rise to LINE-1 chimeric transcripts (LCTs). Here, we show that one such LCT, LCT13, is a large transcript (>300 kb) running antisense to the metastasis-suppressor gene TFPI- 2. We have modelled antisense RNA expression at TFPI-2 in transgenic mouse embryonic stem (ES) cells and demonstrate that antisense RNA induces silencing and deposition of repressive histone modifications implying a causal link. Consistent with this, LCT13 expression in breast and colon cancer cell lines is associated with silencing and repressive chromatin at TFPI-2. Furthermore, we detected LCT13 transcripts in 56% of colorectal tumours exhibiting reduced TFPI-2 expression. Our findings implicate activation of LINE-1 elements in subsequent epigenetic remodelling of surrounding genes, thus hinting a novel retrotransposition-independent role for LINE-1 elements in malignancy

Climate oscillations, glacial refugia, and dispersal ability: factors influencing the genetic structure of the least salmonfly, Pteronarcella badia (Plecoptera), in Western North America

Background: Phylogeographic studies of aquatic insects provide valuable insights into mechanisms that shape the genetic structure of communities, yet studies that include broad geographic areas are uncommon for this group. We conducted a broad scale phylogeographic analysis of the least salmonfly Pteronarcella badia (Plecoptera) across western North America. We tested hypotheses related to mode of dispersal and the influence of historic climate oscillations on population genetic structure. In order to generate a larger mitochondrial data set, we used 454 sequencing to reconstruct the complete mitochondrial genome in the early stages of the project. Results: Our analysis revealed high levels of population structure with several deeply divergent clades present across the sample area. Evidence from five mitochondrial genes and one nuclear locus identified a potentially cryptic lineage in the Pacific Northwest. Gene flow estimates and geographic clade distributions suggest that overland flight during the winged adult stage is an important dispersal mechanism for this taxon. We found evidence of multiple glacial refugia across the species distribution and signs of secondary contact within and among major clades. Conclusions: This study provides a basis for future studies of aquatic insect phylogeography at the inter-basin scale in western North America. Our findings add to an understanding of the role of historical climate isolations in shaping assemblages of aquatic insects in this region. We identified several geographic areas that may have historical importance for other aquatic organisms with similar distributions and dispersal strategies as P. badia. This work adds to the ever-growing list of studies that highlight the potential of next-generation DNA sequencing in a phylogenetic context to improve molecular data sets from understudied groups

Low Temperature Unbalanced Magnetron Deposition of Hard, Wear-Resistant Coatings for Liquid-Film Bearing Applications

The original program for evaluating the tribological properties several different hard coatings for liquid film bearing applications was curtailed when the time for the program was reduced from 3 years to 1. Of the several different coatings originally planned for evaluation, we decided to concentrate on one coating, carbon nitride. At BIRL, we have been instrumental in the development of reactively sputtered carbon nitride coatings, and we have found that it is a very interesting new material with very good tribological properties. In this program, we found that the reactively sputtered carbon nitride does not bond well directly to hardened 440C stainless steel; but if an interlayer of titanium nitride is added between the carbon nitride and the 440C, the adhesion of the dual coating combination is very good. Statistically designed experiments were run with the dual layer combination, and 3 variables were chosen for the Box-Benken design, which were the titanium nitride interlayer thickness, the nitrogen partial pressure during the reactive sputtering of the carbon nitride, and the carbon nitride substrate bias voltage. Two responses were studied from these three variables; the adhesion of the dual coating combination to the 440C substrate and the friction coefficient of the carbon nitride in dry sliding contact with 52100 steel in air. The best adhesion came with the thickness interlayer thickness studied, which was 4 micrometers, and the lowest coefficient of friction was 0.1, which was achieved when the bias voltage was in the range of -80 to - 120 V and the nitrogen partial pressure was 3 mTorr

Application of hard coatings to substrates at low temperatures

BIRL, the industrial research laboratory of Northwestern University, has conducted unique and innovative research, under sponsorship from the NASA Marshall Space Flight Center (MSFC), in the application of hard, wear resistant coatings to bearing steels using the high-rate reactive sputtering (HRRS) process that was pioneered by Dr. William Sproul, the principal investigator on this program. Prior to this program, Dr. Sproul had demonstrated that it is possible to apply hard coatings such as titanium nitride (TiN) to alloy steels at low temperatures via the HRRS process without changing the metallurgical properties of the steel. The NASA MSFC program at BIRL had the specific objectives to: apply TiN to 440C stainless steel without changing the metallurgical properties of the steel; prepare rolling contact fatigue (RCF) test samples coated with binary hard coatings of TiN, zirconium nitride (ZrN), hafnium nitride (HfN), chromium nitride (CrN), and molybdenum nitride (MoN), and metal coatings of copper (Cu) and gold (Au); and develop new alloyed hard coatings of titanium aluminum nitride (Ti(0.5)Al(0.5)N), titanium zirconium nitride (Ti(0.5)Zr(0.5)N), and titanium aluminum vanadium nitride

Observation of the Dynamic Beta Effect at CESR with CLEO

Using the silicon strip detector of the CLEO experiment operating at the Cornell Electron-positron Storage Ring (CESR), we have observed that the horizontal size of the luminous region decreases in the presence of the beam-beam interaction from what is expected without the beam-beam interaction. The dependence on the bunch current agrees with the prediction of the dynamic beta effect. This is the first direct observation of the effect.Comment: 9 page uuencoded postscript file, postscritp file also available through http://w4.lns.cornell.edu/public/CLNS, submitted to Phys. Rev.

A General Equilibrium Theory of Contracts in Community Supported Agriculture

Community Supported Agriculture (CSA) contracts allow consumers to buy claims on a farm\u27s future production. In turn, the consumer provides working capital to the farm during the growing season. CSA contracts also provide risk management for farmers with limited access to Federal crop insurance by transferring part of the farm\u27s risk to the consumer. We derive a theory of CSA contract pricing for the two most prevalent types of CSA contracts: yield contracts, in which consumers receive a percentage of the farm\u27s production, and weight contracts, in which consumers receive fixed quantities. We develop a two-period model in which expected utility maximizing producers and consumers engage in CSA contracting in the first period based on anticipation of yields and spot prices in the second period. Using the model, we generate several testable hypotheses to be explored in future research. Additionally, we present an overview of the data necessary to test the propositions and potential challenges that might arise in related empirical work

Using human disease mutations to understand de novo DNA methyltransferase function.

DNA methylation is a repressive epigenetic mark that is pervasive in mammalian genomes. It is deposited by DNA methyltransferase enzymes (DNMTs) that are canonically classified ashaving de novo (DNMT3A and DNMT3B) or maintenance (DNMT1) function. Mutations in DNMT3A and DNMT3B cause rare Mendelian diseases in humans and are cancer drivers. Mammalian DNMT3 methyltransferase activity is regulated by the non-catalytic region of the proteins which contain multiple chromatin reading domains responsible for DNMT3Aand DNMT3B recruitment to the genome. Characterising disease-causing missense mutations has been central in dissecting the function and regulation of DNMT3A and DNMT3B. These observations have also motivated biochemical studies that provide the molecular details as to how human DNMT3A and DNMT3B mutations drive disorders. Here, we review progress in this area highlighting recent work that has begun dissecting the function of the disordered N-terminal regions of DNMT3A and DNMT3B. These studies haveelucidated that the N-terminal regions of both proteins mediate novel chromatinrecruitment pathways that are central in our understanding of human disease mechanisms.We also discuss how disease mutations affect DNMT3A and DNMT3B oligomerisation, a process that is poorly understood in the context of whole proteins in cells. This dissection of de novo DNMT function using disease-causing mutations provides a paradigm of how genetics and biochemistry can synergise to drive our understanding of the mechanisms through which chromatin misregulation causes human diseas

The Pricing of Community Supported Agriculture Shares: Evidence from New England

Purpose: Community Supported Agriculture (CSA) programs allow consumers to buy a share of a farm’s production while providing working capital and risk management benefits for farmers. Several different types of CSA arrangements have emerged in the market with terms varying in the degree to which consumers share in the farm’s risk. No-arbitrage principles of futures and options pricing suggest that CSA shares should be priced to reflect the degree of risk transfer. Methodology: We evaluate the three most common share types using a cross-sectional dataset of 226 CSA farms from New England to determine if there is empirical evidence in support of the theoretical price relationship between share types. Findings: The degree of risk transfer from farmers to consumers has a significant effect on the share price. There are statistically significant returns to scale and higher prices for organics. Farm characteristics and product offerings predict which type of shares is offered for sale. Research limitations: The data set does not contain information pertaining to actual deliveries, expected deliveries, variance of expected deliveries, or covariance information; thus differences in share prices could be due to differences in these uncontrolled factors. Value: This paper provides empirical evidence that CSA share prices reflect the degree of risk transferred from the producer to the consumer. It also highlights challenges in conducting empirical work pertaining to CSA contracting

Academic Collective Bargaining: Patterns and Trends

Educational services, particularly higher education, has slowly and methodically become one of the most heavily unionized segments, with much greater representation than traditional labor segments. Despite these changes, the increase in academic collective bargaining has not been well documented. Consequently, the purpose of the current paper is to examine recent trends in academic collective bargaining and to compare these trends with the current unionization and collective bargaining situation in other major industries in the United States. We begin with a comparative analysis of unionization in the United States by industry. The summary data we present indicate that the educational services industry is the third largest industry category in the United States and is the most highly unionized industry in the nation. Next, we tighten our focus to examine recent patterns and trends in academic collective bargaining. The data suggest that colleges and universities are a major sector in the overall employment landscape of the United States with academic collective bargaining representing one of the most important growth segments within the U.S. labor movement. In short, higher education unionization is expanding at a faster rate than overall union growth with the expansion of graduate student employee unionization as an area of special interest